RESUMO
Secondary acute myeloid leukemia (sAML) traditionally has inferior outcomes compared to de novo AML. Allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy. This study analyzes the outcomes for unmanipulated haploidentical HCT (haploHCT) for sAML using the Acute Leukemia Working Party (ALWP) registry of the European Society for Blood and Marrow Transplantation (EBMT). We identified 154 patients with sAML who underwent haploHCT from 2006 to 2016. Median age at HCT was 60 years with time from diagnosis to HCT 5 months. At transplantation, 69 patients were in first CR and 85 had active disease. Fifty-seven (38.0%) patients underwent myeloablative conditioning and 97 (62.0%) reduced intensity conditioning (RIC) conditioning. Multivariate analysis showed that there was no difference in RI, nonrelapse mortality (NRM), leukemia free survival (LFS), overall survival (OS), or GVHD-free/relapse free survival (GRFS) for conditioning intensity, age, performance status, or graft source. Active disease was associated with higher RI and inferior LFS, OS, and GRFS compared with patients in CR at time of transplant. T-cell depletion with anti-thymoglobulin resulted in higher NRM and inferior LFS, OS, and GRFS compared to post-transplant cyclophosphamide (PTCy) (HR 2.25, 2.01, 2.16, and 1.73, respectively with P values <.05). Our data shows that haploHCT is a feasible alternative for sAML when matched transplantation is unavailable.
Assuntos
Leucemia Mieloide Aguda/terapia , Transplante Haploidêntico/métodos , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Depleção Linfocítica/métodos , Depleção Linfocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
PURPOSE: Bloodstream infections (BSIs) are frequent after allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to identify predictors of mortality after BSI in patients who undergo HSCT. METHODS: Patients who underwent HSCT between 1 January 2004 and 31 January 2008 and developed BSI during the first year post-transplantation were included. Variables influencing overall mortality at 7 and 30 days after BSI were analysed. RESULTS: BSIs developed in 149 patients, within a median of 9 days after undergoing HSCT. Early and late mortality were 15 and 27%, respectively. Of the BSI, 54% were due to Gram-positive microorganisms, 33% were due to Gram-negative microogranisms, 10% were polymicrobial and 3% were fungal. The associated 7-and 30-day mortality was respectively 10 and 24% (Gram positive), 22 and 31% (Gram negative; Pseudomonas aeruginosa mortality 67%, all within 7 days), 13 and 27% (polymicrobial) and 40% (fungal, all within 7 days). Early mortality was higher in relapsed disease at HSCT (25.9%, p = 0.01), but lower in early (i.e. within 20 days of HSCT) BSI (11.7%, p = 0.03) and BSI due to Gram-positive infective agents (10%, p = 0.05). Multivariate analysis confirmed a higher mortality in late BSI [odds ratio (OR) 3.29, p = 0.03] and relapsed disease at HSCT (OR 2.2, p = 0.04). Late mortality was associated with the type of underlying disease (OR 0.44 for diseases other than acute leukaemia, p = 0.05) and its status (OR 6.04 for relapse at HSCT, p = 0.001). Appropriate empirical therapy was associated with lower early and late mortality in single Gram-negative BSI (16 vs. 45% for 7-day mortality, p = 0.09; 21 vs. 64% for 30-day mortality, p = 0.02). CONCLUSIONS: BSIs are frequent during the first year after HSCT and are associated with a high mortality rate. The aetiology influenced early mortality, while the type and phase of the underlying disease played a pivotal role in late mortality. Appropriate empirical therapy is crucial in BSI due to Gram-negative infective agents.
Assuntos
Bacteriemia/mortalidade , Coinfecção/mortalidade , Fungemia/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bactérias/isolamento & purificação , Estudos de Coortes , Coinfecção/epidemiologia , Coinfecção/microbiologia , Feminino , Fungemia/epidemiologia , Fungemia/microbiologia , Fungos/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade , Transplante Homólogo/estatística & dados numéricos , Adulto JovemRESUMO
Bacteremia is a well known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients and enterococci are among the most frequently isolated pathogens. The aim of this study was to identify risk factors for enterococcal bacteremia during the first 30 days after allogeneic HSCT. A retrospective case-control study was performed; for each case, 3 controls were randomly selected among 306 patients transplanted during the study period (January 1, 2004 to December 31, 2007). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for variables influencing the risk for bacteremia. Overall, 33 patients developed enterococcal bacteremia, within a median of 9 days after HSCT (range, 2-24). The cumulative incidence was 10.8%. Multivariate analysis identified the following variables as risk factors for enterococcal bacteremia: donor and transplant type (greater risk for mismatched related or cord blood) (OR=8.98, 95% CI, 1.65-48.99 and OR=7.52, 95% CI, 1.56-36.31, respectively, P=0.047); severe (grades 3-4) mucositis (OR=9.04, 95% CI, 1.97-41.52, P=0.018); pharyngeal enterococcal colonization (OR=4.48, 95% CI, 1.11-18.03, P=0.035); and previous empirical therapy with cephalosporins (OR=4.16, 95% CI, 0.93-18.66 for 1-7 days of therapy, and OR=7.31, 95% CI, 1.78-30.12 for 8-23 days, P=0.018). Higher Karnofsky score (≥50) and previous empirical therapy with glycopeptides were associated with a decreased risk (OR=0.25, 95% CI, 0.06-0.97, P=0.045 and OR=0.11, 95% CI, 0.02-0.59, P=0.010, respectively). The crude mortality at 7 and 30 days was 12% (4/33) and 24% (8/33), respectively. Enterococcal bacteremia is frequent after allogeneic HSCT. The factors associated with this infection are type of transplant, pharyngeal colonization, severe mucositis, and use of cephalosporins. Good general conditions and the use of vancomycin were associated with lower risk of enterococcal bacteremia.
Assuntos
Bacteriemia/epidemiologia , Enterococcus/isolamento & purificação , Infecções por Bactérias Gram-Positivas/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Estudos de Casos e Controles , Cefalosporinas/uso terapêutico , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosite/epidemiologia , Mucosite/microbiologia , Faringe/microbiologia , Fatores de Risco , Transplante Homólogo/efeitos adversos , Vancomicina/uso terapêutico , Adulto JovemRESUMO
Autologous haematopoietic stem-cell transplantation has been evaluated over the last years as a possible new therapeutic strategy in severe forms of multiple sclerosis unresponsive to the approved therapies. Up to now, more than 400 patients have been treated and numerous are the phase I and phase II studies which addressed the feasibility of this treatment, the efficacy, side effects and transplant-related mortality. The clinical response is strongly related to the intensity of the conditioning regimen utilized as well as to the phase of the disease course in which the therapy is carried out. Rapidly evolving multiple sclerosis with a relapsing-remitting clinical course and MRI signs of activity are the cases that can take more advantage. The risk of mortality, which dropped in the last years to 2-3%, is still the main problem of this powerful therapy.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla/terapia , Ensaios Clínicos como Assunto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Resultado do TratamentoRESUMO
Changes in lung volume occur following haematopoietic stem cell transplantation (HSCT); airway hyperresponsiveness was occasionally reported, without mechanistic explanation. The present authors studied 17 patients by standard methacholine (MCh) challenge before and then 3 and 12 months after HSCT (n = 16 and n = 13, respectively). Another 6 patients were challenged before and 3 months after HSCT using a modified challenge to investigate the effect of deep inhalations. No patient developed bronchiolitis obliterans or bronchiolitis obliterans organising pneumonia. At 3 months, forced vital capacity (FVC) was significantly reduced by 0.33+/-0.55 L, forced expiratory volume in one second (FEV(1)) by 0.31+/-0.50 L, total lung capacity (TLC) by 0.39+/-0.37 L and single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) by 15+/-12%. At 12 months, TLC decreased by 0.43+/-0.36 L and D(L,CO )by 8+/-8%. With standard challenge, no significant changes in FEV(1) response to MCh were observed after HSCT but FVC decreased significantly less after HSCT compared with prior to HSCT, suggesting less air trapping. With modified challenge, deep inhalations reversed the MCh-induced decrease in partial expiratory flow more after HSCT compared with before HSCT and this correlated with TLC decrements. In conclusion, an increase in airway responsiveness is unlikely after haematopoietic stem cell transplantation, at least in patients without pulmonary complications, and mechanisms opposing airway narrowing may blunt the bronchoconstrictor response.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pulmão/fisiopatologia , Adulto , Aerossóis/metabolismo , Testes de Provocação Brônquica , Broncoconstritores/farmacologia , Monóxido de Carbono/química , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Masculino , Cloreto de Metacolina/farmacologia , Pessoa de Meia-Idade , Sistema Respiratório , Capacidade Vital/efeitos dos fármacosRESUMO
The aim was to determine whether outcome of unrelated donor transplantation for severe aplastic anemia has improved in recent years and whether this is due to patient selection or better transplant technology. We analyzed 498 patients transplanted during 1990-2005. By running univariate regression models dichotomizing year of transplantation we defined 1998 as the year of the most significant change in survival. Five-year survival increased from 32+/-8% before 1998 to 57+/-8% after 1998 (P<0.0001). When comparing the cohort before (n=149) and after 1998 (n=349), there were no differences except for older age, and more frequent use of PBSCs, after 1998. High-resolution HLA typing data were unavailable. After 1998, there was less graft failure (11 vs 26%, P<0.0001), less acute GvHD (cumulative incidence 28 vs 37%, P=0.02) and less chronic GvHD (22 vs 38%, P=0.004). In multivariate analyses adjusting for differences in age, HLA-mismatch, performance score and time to transplantation, there was no change in the year of transplant effect (relative risk of death in transplants after 1998: 0.44 (95% confidence interval 0.33-0.59)). There is no evidence for patient selection to explain significantly improved survival in patients transplanted after 1998. We speculate that this is due to better donor matching.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Linfocítica Crônica de Células B/terapia , Transplante Haploidêntico , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Haploidêntico/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. METHODS: This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). RESULTS: Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). CONCLUSIONS: IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Micoses/epidemiologia , Complicações Pós-Operatórias/microbiologia , Adolescente , Adulto , Idoso , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Micoses/tratamento farmacológico , Micoses/microbiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We assessed the outcome of 170 patients with AML in first complete remission, aged 1-47 years (median 29), who had undergone an allogeneic BMT before or after 1990 (n=80 and n=90, respectively); all patients were prepared with cyclophosphamide and TBI; the median follow-up for surviving patients was 13 years. The donor was an HLA-identical sibling in 164 patients. Transplant-related mortality (TRM) was 30% before and 7% after 1990 (P<0.001); relapse-related death (RRD) was 26 and 11% (P=0.002); and actuarial 10-year survival was 42 and 79% (P<0.00001). Patients transplanted after 1990 were older, had a shorter interval diagnosis-BMT, had less FAB-M3 cases, received a higher dose of TBI, a higher marrow cell dose and combined (cyclosporine+methotrexate) GVHD prophylaxis. Patients relapsing after transplant had an actuarial survival of 0 vs 31% if grafted before or after 1990 (P=0.01), and their median follow-up exceeds 10 years. In conclusion, the overall survival of first remission AML undergoing an allogeneic BMT has almost doubled in the past two decades, despite older age and fewer M3 cases. Improvement has come not only from changes in transplant procedures, but also from effective rescue of patients relapsing after transplant.
Assuntos
Transplante de Medula Óssea/métodos , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/terapia , Humanos , Lactente , Itália/epidemiologia , Masculino , Recidiva Local de Neoplasia/terapia , Indução de Remissão/métodos , Risco , Análise de Sobrevida , Transplante HomólogoRESUMO
We assessed the long-term outcome of patients with relapsed acute myeloid (n=86) or acute lymphoid leukemia (n=66), undergoing an allogeneic hemopoietic stem cell transplantation in our unit. The median blast count in the marrow was 30%. Conditioning regimen included total body irradiation (TBI) (10-12 Gy) in 115 patients. The donor was a matched donor (n=132) or a family mismatched donor (n=20). Twenty-two patients (15%) survive disease free, with a median follow-up of 14 years: 18 are off medications. The cumulative incidence of transplant related mortality is 40% and the cumulative incidence of relapse related death (RRD) is 45%. In multivariate analysis of survival, favorable predictors were chronic graft-versus-host disease (GvHD) (P=0.0003), donor other than family mismatched (P=0.02), donor age less than 34 years (P=0.02) and blast count less than 30% (P=0.07). Patients with all four favorable predictors had a 54% survival. In multivariate analysis of relapse, protective variables were the use of TBI (P=0.005) and cGvHD (P=0.01). This study confirms that a fraction of relapsed leukemias is cured with an allogeneic transplant: selection of patients with a blast count <30%, identification of young, human leukocyte antigen-matched donors and the use of total body radiation may significantly improve the outcome.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/terapia , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doença Aguda , Adolescente , Adulto , Exame de Medula Óssea , Criança , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide/complicações , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Prognóstico , Sobreviventes , Transplante HomólogoRESUMO
The anti-CD20 chimaeric monoclonal antibody Rituximab has recently been shown to induce significant clinical response in a proportion of patients with refractory chronic graft-versus-host disease (cGVHD). We now report 38 patients, median age 48 years (22-61), receiving Rituximab for refractory cGVHD, assessed for clinical response and survival. Median duration of cGVHD before Rituximab was 23 months (range 2-116), the median number of failed treatment lines was 3 (range 1 to > or =6) and the median follow-up after Rituximab was 11 months (1-88). Overall response rate was 65%: skin 17/20 (63%), mouth 10/21 (48%), eyes 6/14 (43%), liver 3/12 (25%), lung 3/8 (37.5%), joints 4/5, gut 3/4, thrombocytopaenia 2/3, vagina 0/2, pure red cell aplasia 0/1 and, myasthenia gravis 1/1. During the study period 8/38 died: causes of death were cGVHD progression (n=3), disease relapse (n=1), infection (n=3), sudden death (n=1). The actuarial 2 year survival is currently 76%. We confirm that Rituximab is effective in over 50% of patients with refractory cGVHD and may have a beneficial impact on survival.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Fatores Imunológicos/administração & dosagem , Adulto , Anticorpos Monoclonais Murinos , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Transplante de Células-Tronco , Taxa de SobrevidaRESUMO
The first autologous hematopoietic stem cell transplantation in Europe for a patient with severe refractory systemic lupus erythematosus (SLE) was performed in Genoa in 1996. Since then, 32 patients with a wide spectrum of autoimmune diseases (ADs) received autologous transplants, 22 of them with multiple sclerosis (MS). There were no fatal adverse events. All patients had complete or very good partial remissions, but relapses were frequent, especially in SLE, though never as aggressive as pretransplant. The mechanism of action of this intervention remains not completely understood, as briefly discussed here.
Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/cirurgia , Esclerose Múltipla/imunologia , Esclerose Múltipla/cirurgia , Transplante de Células-Tronco , Humanos , Lúpus Eritematoso Sistêmico/patologia , Esclerose Múltipla/patologia , Recidiva , Transplante de Células-Tronco/efeitos adversos , Taxa de Sobrevida , Fatores de TempoRESUMO
Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.
Assuntos
Técnicas de Apoio para a Decisão , Transplante de Células-Tronco Hematopoéticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Anos de Vida Ajustados por Qualidade de VidaRESUMO
More than 40,000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers and many community health-care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Blood and Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors.
Assuntos
Transplante de Células-Tronco Hematopoéticas/normas , Atenção à Saúde/normas , Intervalo Livre de Doença , Europa (Continente) , Feminino , Pessoal de Saúde/normas , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Sociedades Médicas , Estados UnidosRESUMO
A bone marrow harvest is filtered either in the operating room, in the laboratory or during infusion to the patient. Filters are usually discarded. Little is known of haemopoietic progenitor cells (HPCs) trapped in the filters. The aim of the study was to evaluate HPC content in the filters and to assess the outcome of transplants with filter-discarded or filter-recovered cells. Haemopoietic progenitors were grown from filters of 19 marrow transplants. We then compared the outcome of 39 filter-recovered transplants from HLA-identical siblings (years 2001-2004) with a matched cohort of 43 filter-discarded marrow grafts (years 1997-2000). Filters contained on average 21% long-term culture-initiating cells (LTC-IC) and 15% fibroblasts colony-forming units (CFU-F) of the total progenitor cell content. Filter-discarded transplants had significantly more grade II-IV graft-versus-host disease (GvHD) (42 vs 15%, P=0.008) as compared to filter-recovered transplants, and more transplant-related mortality (TRM) (20 vs 3%, P=0.04). The actuarial survival at 5 years is 69 vs 87%, respectively (P=0.15). This study suggests that a significant proportion of LTC-IC is lost in the filters together with CFU-F. Recovery and add back of progenitors trapped in the filters may reduce GvHD and TRM.
Assuntos
Transplante de Medula Óssea/métodos , Filtração/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Células Cultivadas , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To describe molecular monitoring of minimal residual disease in patients with myeloma who have achieved complete remission (CR) after autologous or allogeneic transplantation of hematopoietic cells. MATERIALS AND METHODS: Clonal markers based upon the rearrangement of immunoglobulin heavy-chain genes were generated for each patient and used for polymerase chain reaction (PCR) detection of residual myeloma cells. Fifty-one patients entered the program and 36 achieved CR. After transplantation, molecular monitoring was performed on 29 patients (15 autologous and 14 allogeneic transplants) who had molecular markers. RESULTS: Our data show that molecular remissions are rarely achieved (7%) with high-dose chemotherapy followed by single or double autografting. In addition, virtually all peripheral blood progenitor cell and bone marrow samples contained residual myeloma cells, even when sample collection was scheduled after repeated courses of high-dose chemotherapy. All patients autografted with PCR-positive cells remain positive, and eight of 15 have relapsed. Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive group and one in the PCR-negative group. CONCLUSION: This is the first large study of molecular remissions in myeloma patients to use a PCR-based approach utilizing patient-specific tumor markers. The sizeable fraction of patients who achieved molecular remission after allografting with peripheral blood progenitor cells represents a promising finding in an incurable disease.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Feminino , Rearranjo Gênico , Marcadores Genéticos , Humanos , Região Variável de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Neoplasia Residual , Reação em Cadeia da Polimerase , Indução de Remissão , Análise de Sequência de DNA , Transplante Autólogo , Transplante HomólogoRESUMO
Thirty-eight second allogeneic bone marrow transplants (BMT) for acute leukemia relapsed after first BMT were performed in 13 Italian centers between 1987 and 1994. Twenty-one patients had acute myelogenous leukemia (AML), 17 acute lymphoblastic leukemia (ALL); at second BMT 24 patients were in complete remission (CR) and 14 in relapse. The median time to relapse after first BMT was 10 months (range 1-70). Grade II or greater acute graft-versus-host disease (GVHD) after second transplant occurred in 34.2% of patients and a chronic GVHD in 31.5% of patients. Twenty-four patients died: seven from early transplant-related mortality (TRM), 13 from relapse and four from late toxicity. As of 31 July 1996, at a median follow-up of 47 months (range 22-85), there are 14 survivors. The three-year probability of TRM, relapse and event-free survival (EFS) is 28%, 40% and 42% respectively. In 20 of 27 evaluable patients, remission duration after second BMT was longer than after the first BMT. A diagnosis of AML was correlated with a better outcome. These data support the usefulness of second allograft in selected patients with AML relapsing after a first BMT.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/cirurgia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/imunologia , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Resultado do TratamentoRESUMO
T lymphocytes were derived by E-rosetting techniques from the peripheral blood and bone marrow of 12 healthy donors. Following incubation of 18 h with PWM, PHA, Con-A or culture medium (RPMI) alone, the lymphocytes were harvested by centrifugation and washed. Both lymphocytes and culture supernatants were tested for CFUC suppressor activity in semisolid bone marrow cultures. The results of this study indicate that (a) T cells and supernatants from unstimulated cultures contained no CFUC suppressor activity, (b) T cells and supernatants from cultures stimulated with PHA, PWM or Con-A significantly suppressed autologous and allogeneic bone marrow CFUC, (c) there was no significant difference between the ability of bone marrow or peripheral blood T cells to inhibit CFUC, and (d) mitogens alone had either no effect or a moderate enhancing activity on marrow CFUC. These findings suggest that generation of CFUC suppressor T cells occurs normally within a few hours of polyclonal T cell stimulation.
Assuntos
Células da Medula Óssea , Ensaio de Unidades Formadoras de Colônias , Ativação Linfocitária , Linfócitos T Reguladores/citologia , Concanavalina A/farmacologia , Meios de Cultura , Relação Dose-Resposta Imunológica , Humanos , Linfócitos/citologia , Fito-Hemaglutininas/farmacologia , Mitógenos de Phytolacca americana/farmacologia , Linfócitos T/imunologiaRESUMO
In vitro colony formation (CFUC) was studied in 8 patients with severe aplastic anemia (SAA) in complete hematologic remission following high dose pulse methylprednisolone (P/6-MPr) and/or antilymphocyte globulin (ALG). All patients except one were off maintenance treatment at the time of study, and follow-up ranged from 271 to 630 days. All patients showed marked reduction of colonies (2 +/- 3/2.5 x 10(5) cells; our normal 61 +/- 14) and clusters (77 +/- 45; our normal 179 +/- 83), which persisted for as long as 600 days after initial therapy. Incubation of patients' marrow with ALG did not enhance significantly colony formation. Co-culture of bone marrow from 6 patients with SAA in remission and normal marrow produced a marked inhibition of the expected colonies (84 +/- 16%) and clusters (29 +/- 23%). Incubation of patients' marrow with ALG prior to the co-culture experiments did not prevent suppression of colonies and clusters. Co-culture of patients' peripheral blood lymphocytes with normal marrow had no effect on colony formation. Therefore remission marrow from patients with SAA exhibits severely impaired in vitro growth (CFUC) and marked myelosuppressive activity against normal marrow cells. Incubation of patients' marrow with ALG has no significant effect on either assay.
Assuntos
Anemia Aplástica/patologia , Células-Tronco Hematopoéticas/patologia , Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Células da Medula Óssea , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Humanos , Metilprednisolona/uso terapêutico , Remissão EspontâneaRESUMO
A total of 29 consecutive patients with leukemia or aplastic anemia who received an HLA-identical marrow graft were given cyclosporin A (CyA) to prevent graft-versus-host disease (GvHD). These patients were compared with an historic group of 25 similar patients with leukemia or AA given methotrexate (MTX) for GvHD prophylaxis at this institution. Engraftment was faster in patients given CyA when compared with MTX patients, with less days of granulocytopenia (P = 0.04), a shorter interval before reaching a platelet count of 70 X 10(9)/l (P = 0.04), fewer major infections (P = 0.01), and fewer days on intravenous antibiotics (P = 0.02). There were no graft failures in CyA patients compared with four of 25 in MTX patients (P = 0.01). Early mortality was lower in CyA patients but not significantly (P = 0.06). The incidence of pulmonary complications was comparable, five of 29 and seven of 25 in CyA and MTX patients, respectively, but the clinical features of such complications differed. Interstitial pneumonia developing after day 30 was seen in MTX patients, whereas an acute respiratory distress syndrome developing between day +8 and day +18 was seen in CyA patients. Acute GvHD was less severe in CyA patients (P = 0.04), but chronic GvHD was comparable (P = 0.3). The actual one-year survival is currently 72% and 52% in CyA and MTX patients, respectively (P = 0.1). Although our initial experience with CyA is encouraging with regard to engraftment and acute GvHD, optimization of CyA protocols will probably be needed for it to be proven as having a definite advantage over MTX.